Search Results (13)

Background: Sepsis is a major global health issue and the leading cause of death in critically ill patients, with rising incidence and associated healthcare costs. Early administration of antibiotic therapy is crucial, but increasing antibiotic resistance poses a threat. Beta-lactam antibiotics, commonly used as a first-line therapy option against sepsis, often demonstrate unpredictable concentrations due to pharmacokinetic and pharmacodynamic changes in critically ill patients. Acute kidney injury (AKI) affects a significant portion of septic patients, and continuous renal replacement therapy can further complicate treatment by reducing antibiotic levels and, consequently, increasing antibiotic resistance risk. Objectives: To develop pharmacokinetic/pharmacodynamic models for beta-lactam antibiotics in septic shock patients undergoing continuous renal replacement therapy (CRRT), with the goal of optimizing antibiotic dosing and then improving treatment outcomes. Methods: Septic shock Caucasian adult patients treated with beta-lactams and who have undergone major surgery in AKI failure that requires CRRT will be eligible with previous informed written consent. CRRT will be performed exclusively using Continuous Venovenous Hemodiafiltration (CVVHDF) modality. Antimicrobial determination analyses will be carried out with LC-MS/MS. Further calculation of pharmacokinetic parameters and determination of PK/PD breakpoints will be made using Monte Carlo simulation. Conclusions: The expected results from this study will lead to a better understanding of the pharmacokinetics of beta-lactam antibiotics in critically ill patients with AKI and septic shock undergoing CVVHDF, allowing for improved therapeutic strategies. Full article

Objective: To explore the synergistic effect of HA380 hemoperfusion adsorbent combined with continuous veno-venous hemodiafiltration (CVVHDF) in the treatment of septic shock. Patients and methods: This retrospective study included 56 adult septic shock patients who underwent blood purification treatment in the Surgical Intensive Care Unit (SICU) of Third Affiliated Hospital of Sun Yat-sen University from 1 September 2022 to 1 April 2024. Twenty patients received a combination therapy of HA380 hemoperfusion and CVVHDF, while 36 patients received only CVVHDF treatment. Inflammatory markers such as white blood cells (WBC), procalcitonin (PCT), and interleukin-6 (IL-6) were evaluated. Changes in acute physiology and chronic health status evaluation system (APACHE II) scores, sequential organ failure (SOFA) scores, and outcomes at 7 and 28 days after treatment were recorded. Result: After 24 h of treatment, the levels of PCT and IL-6 in the combined group decreased significantly (p < 0.05). The 7-day and 28-day mortality rates of the combined group were 25% and 30%, respectively, while the mortality rates of the CVVHDF group were 27.8% and 50%, respectively. Conclusion: HA380 hemoperfusion combined with CVVHDF was safe and effective in treating patients with septic shock. Full article

Background: Renal replacement therapy with an oXiris hemofilter may be helpful for patients with acute kidney injury in conjunction with sepsis and septic shock. The aim of this study was to assess the impact of an oXiris membrane on septic shock patients. Methods: All renal replacement therapies with oXiris (Baxter, Deerfield, IL, USA) performed between January 2018 and August 2021 were retrospectively analyzed. CRRT was initiated in continuous venovenous hemodiafiltration (CVVHDF) mode using Prismaflex System (Baxter). Demographic data, starting point of infection, source control, etiology, and course of treatment were analyzed. Results: A total of 32 patients were included in the study. Most patients treated with oXiris had acute kidney injury (AKI) and required CRRT. One patient had KDIGO 1 AKI (3.1%), three patients (9.4%) had KDIGO 2 AKI, and 28 patients (87.5%) had KDIGO 3 AKI. A statistically significant decrease in vasopressin dosage was required to achieve adequate MAP after 24 and 72 h, and a statistically significant decrease in norepinephrine dosage after 72 h was observed, with no SOFA score change on days 2 and 3. Procalcitonin and lactate levels did not change after 24 and 72 h. No beneficial effect on mortality was observed. Conclusions: Treatment with an oXiris membrane can positively impact vasopressors’ requirement but not influence SOFA score, procalcitonin or lactate levels, or mortality in septic shock patients. Full article

Introduction: Acute kidney injury (AKI) significantly disrupts vital renal functions and is a common and serious condition in intensive care units (ICUs). AKI leads to extended hospital stays, increases mortality rates, and often necessitates nephrology consultations. Continuous renal replacement therapy (CRRT) plays a central role in managing AKI, requiring a multidisciplinary approach involving nephrologists, intensivists, and anesthesiologists. This study examines the clinical profile and progression of AKI in ICU patients requiring CRRT, with a focus on CRRT indications and modalities. Materials and Methods: We conducted a single-center retrospective observational study on ICU patients with AKI requiring CRRT from January to December 2019. AKI diagnosis followed the RIFLE criteria, and patients who received CRRT for less than 36 h were excluded. Data collected included demographics, hemodynamic parameters, and renal function parameters, with follow-ups at 1 week, 1 month, 6 months, and 12 months. Statistical analyses evaluated outcomes and transitions between CRRT and other renal replacement therapies. Results: Among 123 evaluated patients, 95 met inclusion criteria. Fifteen patients received CRRT for less than 36 h, with an early mortality rate of 80%. The final cohort comprised 80 patients who underwent CRRT for over 36 h, with a mean age of 65.3 years (SD = 13.6) and a Charlson index of 6.4. Patients were categorized based on primary diagnosis into heart failure, cardiac surgery, sepsis, other surgeries, and miscellanea groups. Mortality rates were highest in the heart failure and miscellanea groups. Significant variability was observed in therapy transitions and long-term outcomes. Continuous venovenous hemodiafiltration (CVVHDF) was the most frequently used CRRT modality. Conclusions: This study highlights the variability in CRRT practices and the poor prognosis for critically ill patients with AKI requiring CRRT. Timely nephrology consultation and tailored treatment plans may improve patient outcomes and optimize CRRT utilization. Future research should focus on refining CRRT protocols and exploring preventive strategies for AKI. Full article

(1) Objectives: to describe the pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) meropenem in critical patients with documented Gram-negative infections undergoing continuous veno-venous hemodiafiltration (CVVHDF) and to assess the relationship with microbiological outcome. (2) Methods: Data were retrospectively retrieved for patients admitted to the general and the post-transplant intensive care units in the period October 2022–May 2023 who underwent CVVHDF during treatment with CI meropenem optimized by means of a real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) program for documented Gram-negative infections. Steady-state meropenem plasma concentrations were measured, and the free fractions (fC_ss) were calculated. Meropenem total clearance (CL_tot) was calculated at each TDM assessment, and the impact of CVVHDF dose intensity and of residual diuresis on CL_tot was investigated by means of linear regression. Optimal meropenem PK/PD target attainment was defined as an fC_ss/MIC ratio > 4. The relationship between meropenem PK/PD target attainment and microbiological outcome was assessed. (3) Results: A total of 24 critical patients (median age 68 years; male 62.5%) with documented Gram-negative infections were included. Median (IQR) meropenem fC_ss was 19.9 mg/L (17.4–28.0 mg/L). Median (IQR) CL_tot was 3.89 L/h (3.28–5.29 L/h), and median (IQR) CVVHDF dose intensity was 37.4 mL/kg/h (33.8–44.6 mL/kg/h). Meropenem dosing adjustments were provided in 20 out of 24 first TDM assessments (83.3%, all decreases) and overall in 26 out of the 51 total ECPA cases (51.0%). Meropenem PK/PD target attainment was always optimal, and microbiological eradication was achieved in 90.5% of assessable cases. (4) Conclusion: the real-time TDM-guided ECPA program was useful in attaining aggressive PK/PD targeting with CI meropenem in critically ill patients undergoing high-intensity CVVHDF and allowed microbiological eradication in most cases with dosing regimens ranging between 125 and 500 mg q6h over 6 h. Full article

Lactic acidosis is characterized by an excessive production of lactic acid or by its impaired clearance. Thiamine deficiency is an uncommon cause of lactic acidosis, especially in countries where malnutrition is rare. We describe the case of a 5-year-old boy who presented with a central nervous system relapse of acute lymphoblastic leukemia. During the chemotherapy regimen, the patient developed drug-induced pancreatitis with paralytic ileus requiring prolonged glucosaline solution infusion. In the following days, severe lactic acidosis (pH 7.0, lactates 253 mg/dL, HCO3- 8 mmol/L) was detected, associated with hypoglycemia (42 mg/dL) and laboratory signs of acute liver injury. Due to the persistent hypoglycemia, the dextrose infusion was gradually increased. Lactates, however, continued to raise, so continuous venovenous hemodiafiltration was started. While lactates initially decreased, 12 h after CVVHDF suspension, they started to raise again. Assuming that it could have been caused by mitochondrial dysfunction due to vitamin deficiency after prolonged fasting and feeding difficulties, parenteral nutrition and thiamine were administered, resulting in a progressive reduction in lactates, with the normalization of pH during the next few hours. In the presence of acute and progressive lactic acidosis in a long-term hospitalized patient, thiamine deficiency should be carefully considered and managed as early as possible. Full article

Background: Critically ill patients frequently require continuous renal replacement therapy (CRRT). During CRRT, particles up to 10 kDa in size, such as enoxaparin, may be removed. The aim of this study was to determine if patients receiving prophylactic doses of enoxaparin and treated with continuous veno-venous hemodiafiltration (CVVHDF) reach prophylactic values of anti-Xa factor activity. Methods: In this observational trial, we compared two groups: 20 patients treated with CVVHDF and 20 patients not treated with CVVHDF. All of them received prophylactic doses of 40 mg of enoxaparin subcutaneously. Anti-Xa factor activity was determined on the third day of receiving a prophylactic dose of enoxaparin. The first blood sample was taken just before the administration of enoxaparin, and other samples were taken 3 h, 6 h, and 9 h after the administration of a prophylactic dose of enoxaparin. Results: At 3 and 6 h after administration of enoxaparin in both groups, we observed a significant increase in anti-Xa factor activity from baseline, with the peak after 3 h of administration. There were no significant differences in the numbers of patients who had anti-Xa factor activity within the prophylactic range between CVVHDF and control groups. Conclusion: CVVHDF has only a mild effect on the enoxaparin prophylactic effect measured by anti-Xa factor activity. Thus, it seems there is no need to increase the dose of enoxaparin for patients requiring CVVHDF. Full article

Hyperuricemia is a well-known cardiovascular risk factor. The aim of our study was to investigate the connection between postoperative hyperuricemia and poor outcomes after elective cardiac surgery compared to patients without postoperative hyperuricemia. In this retrospective study, a total of 227 patients after elective cardiac surgery were divided into two groups: 42 patients with postoperative hyperuricemia (mean age 65.14 ± 8.9 years) and a second group of 185 patients without it (mean age 62.67 ± 7.45 years). The time spent on mechanical ventilation (hours) and in the intensive care unit (days) were taken as the primary outcome measures while the secondary measure comprised postoperative complications. The preoperative patient characteristics were similar. Most of the patients were men. The EuroSCORE value of assessing the risk was not different between the groups nor the comorbidities. Among the most common comorbidities was hypertension, seen in 66% of all patients (69% in patients with postoperative hyperuricemia and 63.7% in those without it). A group of patients with postoperative hyperuricemia had a prolonged time of treatment in the intensive care unit (p = 0.03), as well as a prolonged duration of mechanical ventilation (p < 0.01) and a significantly higher incidence of the following postoperative complications: circulatory instability and/or low cardiac output syndrome (LCOS) (χ2 = 4486, p < 0.01), renal failure and/or continuous venovenous hemodiafiltration (CVVHDF’s) (χ2 = 10,241, p < 0.001), and mortality (χ2 = 5.22, p < 0.01). Compared to patients without postoperative hyperuricemia, elective cardiac patients with postoperative hyperuricemia have prolonged postoperative treatment in intensive care units, extended durations of mechanically assisted ventilation, and a higher incidence of postoperative circulatory instability, renal failure, and death. Full article

Leptospirosis is an ubiquitous zoonosis with significant morbidity and mortality. Approximately 10 percent of human infections evolve into a severe form, with a sepsis-like disease, multiorgan failure, and significant mortality rate. The cornerstone of treatment of severe disease is antibiotic therapy, with the aims of preventing complications, reducing the duration of disease, and ultimately reducing mortality. The initiation of antibiotic chemotherapy can precipitate a febrile inflammatory reaction, also known as a Jarisch–Herxheimer reaction. We present a case report of a patient with severe leptospirosis, complicated by multiorgan failure with severe circulatory failure of distributive and cardiogenic etiology, possibly as a consequence of the Jarisch–Herxheimer reaction. The patient was treated with antimicrobial therapy and other supportive measures along with high-dose corticosteroid therapy, long-term mechanical ventilation, high-dose vasopressor therapy, and continuous veno-venous hemodiafiltration with extracorporeal cytokine removal.With this case, we would like to report on a patient presenting with two neglected diseases in our part of Europe, who was treated with novel therapeutic strategies. Full article

The dosage regimen of vancomycin, teicoplanin and daptomycin remains controversial for critically ill patients undergoing continuous renal replacement therapy (CRRT). Monte Carlo simulation was applied to identify the optimal regimens of antimicrobial agents in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections based on the mechanisms of different CRRT modalities on drug clearance. The optimal vancomycin dosage for patients received a CRRT doses ≤ 30 mL/kg/h was 20 mg/kg loading dose followed by 500 mg every 8 h, while 1 g every 12 h was appropriate when 35 mL/kg/h was prescribed. The optimal teicoplanin dosage under a CRRT dose ≤ 25 mL/kg/h was four loading doses of 10 mg/kg every 12 h followed by 10 mg/kg every 48 h, 8 mg/kg every 24 h and 6 mg/kg every 24 h for continuous veno-venous hemofiltration, continuous veno-venous hemodialysis and continuous veno-venous hemodiafiltration, respectively. When the CRRT dose increased to 30–35 mL/kg/h, the teicoplanin dosage should be increased by 30%. The recommended regimen for daptomycin was 6–8 mg/kg every 24 h under a CRRT dose ≤ 25 mL/kg/h, while 8–10 mg/kg every 24 h was optimal under 30–35 mg/kg/h. The CRRT dose has an impact on probability of target attainment and CRRT modality only influences teicoplanin. Full article

Angiotensin-converting enzyme 2 (ACE2) receptor of severe acute respiratory syndrome coronavirus 2 is involved in baroreflex control mechanisms. We hypothesize that severe coronavirus infectious disease 2019 (COVID-19) patients may show an alteration in baroreflex-mediated heart rate changes in response to arterial hypotension. A pilot study was conducted to assess the response to hypotension in relation to continuous venovenous hemodiafiltration (CVVHDF) in critically ill patients with PCR-confirmed COVID-19 (from February to April 2020) and in critically ill non-COVID-19 patients with sepsis (from February 2018 to February 2020). The endpoint was a change in the heart rate in response to CVVHDF-induced hypotension. The association between COVID-19 status and heart rate change was estimated using linear regression. The study population included 6 COVID-19 patients (67% men; age 58 (53–64) years) and 12 critically ill non-COVID-19 patients (58% men; age 67 (51–71) years). Baseline characteristics, laboratory findings, hemodynamic parameters, and management before CVVHDF-induced hypotension were similar between the two groups, with the exception of a higher positive end-expiratory pressure and doses of propofol and midazolam administered in COVID-19 patients. Changes in the heart rate were significantly lower in COVID-19 patients as compared to critically ill non-COVID-19 patients (−7 (−9; −2) vs. 2 (2;5) bpm, p = 0.003), while the decrease in mean arterial blood pressure was similar between groups. The COVID-19 status was independently associated with a lower change in the heart rate (−11 (−20; −2) bpm; p = 0.03). Our findings suggest an inappropriate heart rate response to hypotension in severe COVID-19 patients compared to critically ill non-COVID-19 patients. Full article

The urea cycle is a series of metabolic reactions that convert ammonia into urea in order to eliminate it from the body. Urea cycle disorders are characterized by hyperammonemia, which can cause irreversible damages in central nervous system. We report a series of three newborns presenting irritability, poor feeding and tachypnea. Their first gas analysis revealed respiratory alkalosis. Hyperammonemia was confirmed, and three different enzymatic blocks in the urea cycle were diagnosed. Immediate treatment consisted in the removal of ammonia by reduction of the catabolic state, dietary adjustments, use of nitrogen scavenging agents and ultimately hemodiafiltration. Hyperammonemia is a medical emergency whose treatment should not be delayed. This report aims to highlight the importance of suspecting urea cycle disorders in newborns with aspecific signs of hyperammonemia and respiratory alkalosis, and to sum up the broad lines of hyperammonemia management. Full article

Continuous renal replacement therapy (CRRT) has been used as an important intervention in critically ill children. Our center has the only specialized CRRT team (SCT) for children in Korea, which consists of pediatric intensivists, a pediatric nephrologist and CRRT-specialized-nurses. This study was a retrospective single-center analysis, including all pediatric patients admitted to the intensive care unit (ICU) of Severance hospital in Korea and received CRRT between 2003 and 2016, grouped as before SCT (group A, n = 51) and after SCT (group B, n = 212). We obtained the data for sex, age, weight, diagnosis, blood flow rate or type of CRRT machine used, administration of inotropic agents or anticoagulants, and ICU duration before CRRT (hours). A total of 263 patients were included. The age was significantly younger (p < 0.001) and blood flow rate was lower (p = 0.001) in group B than group A. Vasopressors (p < 0.001), continuous veno-venous hemodiafiltration (CVVHDF) (p < 0.001), nafamostat mesilate (p < 0.001), and extracorporeal membrane oxygenation (ECMO)-CRRT (p = 0.004) were more frequently used in group B. Based on our 14-year experience, we conclude that SCT operation could have played an important role in increasing the amount of CRRT utilization. Full article